The objective of the proposed research is to determine the mechanism of action of phencyclidine (PCP) within the central nervous system. Using electrophysiological techniques, such as the recording of field potentials and single-unit activity, electrical stimulation and iontophoresis, we propose to determine which characteristics of neuronal physiol gy are altered by the drug. This work, performed on rats, will focus on various mechanisms of synaptic transmission (pre- and postsynaptic events, uptake, catabolism of transmitter, receptor interaction). Additional experiments will also determine the possible action of PCP on excitability, axonal conduction and other aspects of neuronal physiology. The following neuronal mechanisms have been selected for investigation in light of recent biochemical findings, as well as reports of specific somesthetic and behavioral effects induced by the drug: (1) Somatosensory mechanisms and peptidic neurotransmission will be investigated as a result of the observed deficit in somesthesia produced by PCP. Specifically, the effects of PCP on neurotransmission at the level of the cuneate nucleus will be determined as well as in pain-related pathways, such as the dorsal horn, reticular formation and the posterior ventrobasal nucleus. (2) Cholinergic and monoaminergic neurotransmission will be studied. The possibility that PCP interferes with these synaptic mechanisms has been suggested by the psychotomimetic and hallucinogenic properties of the drug and also by observed modifications in monoamine uptake and turnover in the presence of PCP.